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Wilms tumour – the surgical issues
SYMPOSIUM: ONCOLOGY
Wilms tumour e the surgical issues
receive regular USS scans of their kidneys. Thus, asymptomatic tumours may be identified at an early stage. Rarely the tumour may rupture following relatively minor trauma e or present as cardiac arrhythmia or fatal pulmonary embolus e see Figure 2.
Simon N Huddart
Differential diagnosis Whilst 90% of the renal tumours of childhood are Wilms, rhabdoid tumour and clear cell carcinoma may also occur. The prognosis for these two latter is worse than that for Wilms, but the surgery is essentially the same. Diagnosis should be confirmed by Trucut biopsy to ensure appropriate chemotherapy regimens are employed. Congenital mesoblastic nephroma accounts for 2% of renal tumours, usually in infancy and carries a good prognosis following successful surgery. Xanthogranulomatous pyelonephritis (XGP) is a benign chronic inflammation of the kidney, which may present with fever and anaemia. The renal mass can usually be distinguished from Wilms tumour on ultrasound, but a Trucut biopsy may be required. One criticism of the original SIOP guidelines (Chemotherapy without biopsy) was that chemotherapy was given prior to open surgery without prior Trucut biopsy. A very small number of XGP cases or clear cell tumours etc were therefore liable to be erroneously treated. Other tumours which may present as a right renal mass include: Neuroblastoma e urinary catecholamines are usually raised. Hepatoblastoma e should be identifiable on USS. Teratoma e may have raised Alfa feto-protein and/or HCG. Whilst benign conditions such as Pelviureteric junction obstruction may present as a large renal mass, a USS should distinguish these from malignancy.
Abstract Complete surgical excision is an essential component of the management of Wilms tumour. With successful surgery, complications should be below 10% and overall survival over 90%. Such surgery may be challenging and should be concentrated to those few surgeons in the UK who perform more than five or six cases per year.
Keywords CCLG; excision; nephrectomy; nephroblastoma; SIOP; Wilms
Introduction Nephroblastoma was first described by Max Wilms in 1899. Before multimodal therapy, surgery was the only option and survival rates were fewer than one in five. Despite the introduction of effective chemotherapy and radiotherapy (for advanced stages) surgery still remains an essential element of the management. Today with surgery and adjuvant chemo/radiotherapy, survival is over 87%. Per and perioperative deaths are very rare except when large tumours present ruptured following trauma. Surgery for a Wilms tumour is seldom an emergency and can be challenging. The most experienced oncological specialist paediatric surgeon available should undertake it and care of the child should be under a multidisciplinary paediatric oncology team.
Diagnosis The majority of Wilms tumours are asymptomatic for the early course of the disease e thus the tumours may present very large. Often it is the parent or clinician who identifies a large lateral mass during bath time or routine examination respectively. Like several of the large tumours of infancy, Nephroblastoma may present as malaise and loss of energy with a slowly enlarging abdominal mass e late or mis-diagnosis is not uncommon. Less commonly, haematuria (15%), abdominal pain (10%) fever (20%) or hypertension (10%) is the presenting complaint. Classically also, a left Wilms tumour may present as a left varicocele due to tumour effects on the renal vein (into which the gonadal vein is a tributary) e see Figure 1. Children with predisposing conditions such as Beckwithe Wiedermann, hemihypertrophy, Aniridia (Wilms tumour, aniridia, genitourinary anomalies, mental retardation e WAGR) or Denys Drash (nephrotic syndrome, ambiguous genitalia) should
Pre-op investigations Oncological USS e usually correctly identifies the Wilms diagnosis. Pre-operative plain chest X-ray in two planes (pulmonary metastases). CT e further identifies pulmonary metastases, confirms normality of contralateral kidney, may identify nephroblastomatosis, should identify venous tumour extension Figure 3. MRI e further delineates venous extension. AFP/HCG e to exclude malignant teratoma. 24 hour Urinary catecholamines e to exclude neuroblastoma. Trucut biopsy This is strongly advised in the UK to obtain tissue diagnosis prior to pre-operative chemotherapy (usually 6 weeks). Several cores of 12e14G are recommended under USS control. Consideration should be given to siting the biopsy entry wound where it can be excised in the nephrectomy procedure.
Simon N Huddart MA MBBS FRCS FRCS(Paeds) Consultant Paediatric Surgeon, Department of Paediatric Surgery, University Hospital of Wales, Cardiff, UK. Conflict of interest: none declared.
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Figure 3 CT scan of large left sided Wilms tumour e no venous involvement is shown.
The trial favoured prior treatment with chemotherapy e intraoperative rupture was reduced from 15% to essentially zero, there was less blood loss and stage II and III tumours were downgraded. In the USA, surgery is performed as initial management of the tumour, and then chemotherapy/radiotherapy is given dependant on stage and histology. The advantage is that a “true” stage of tumour at presentation is achieved and histology is not affected by prior chemotherapy. The main disadvantages are an increase in the risk of tumour rupture at surgery, which can upstage a stage I tumour to stage III. Gow et al recently reported the results of the Children’s Oncology Group renal tumours committee. Of 1,131 primary nephrectomies, tumour spill occurred in 9.7%, with an additional 1.8% having possible spill during renal vein or IVC tumour nephrectomy. Large tumours (more than12 cm) and those on the right were more at risk. As surgery is only an emergency in the rare cases of tumour rupture with uncontrolled bleeding, in the majority of cases, surgery should be a planned procedure by the most experienced surgical team available. The surgeon should make themselves familiar with the various aspects of the SIOP surgical protocol prior to the operation: Computerized tomography e CT and ultrasound scans of the tumour(s) should be studied prior to the operation. In particular, any suspicious hilar or para-aortic lymph nodes should be noted with a view to excision biopsy. Also, any tumour involvement of the renal vein or IVC should be identified (vide infra).
Figure 1 A left sided varicocele in a 2-year-old boy with a large left sided Wilms tumour.
In the United Kingdom and most of Europe, the protocol of SIOP (Societe Internationale Oncologie D’Pediatrique) will be followed. In this protocol, the diagnosis of Wilms and whether it is favourable or unfavourable histology is first confirmed by Trucut biopsy samples taken under ultrasound guidance. The chemotherapy regimen is given pre resection appropriate to the tumour stage and histology. (Fine needle aspiration or Trucut biopsy does not upstage the tumour). A 10-year-trial in the United Kingdom was completed in 2001. UKW3 randomizing early stage Wilms to primary surgery or surgery post 6 weeks of Vincristine.
Staging of Wilms tumour Stage I The tumour is limited to the kidney or surrounded with a fibrous capsule if outside the normal contours of the kidney. The renal capsule or pseudocapsule may be infiltrated with the tumour but it does not reach the outer surface, and it is completely resected (resection margins “clear’) The tumour may be protruding (“bulging’) into the pelvic system and “dipping’ into the ureter (but it is not infiltrating their walls)
Figure 2 Post mortem finding of a massive Wilms tumour embolus.
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The vessels of the renal sinus are not involved Intrarenal vessel involvement may be present Fine needle aspiration or percutaneous core needle biopsy (Trucut) does not upstage the tumour. The presence of necrotic tumour or chemotherapy-induced change in the renal sinus and/or within the peri-renal fat should not be regarded as a reason for upstaging a tumour providing it is completely excised and does not reach the resection margins.
Except in the rare case of tumour rupture, the nephrectomy is an elective operation and should be carried out by the most experienced surgical team. A generous transverse, transperitoneal abdominal incision on the side of the tumour is recommended e although if the CT scan clearly shows no involvement of the contralateral side, it is no longer necessary to physically explore the other kidney. The needle tract of the Trucut biopsy site should be included in the surgical wound resection. The abdomen should be examined for liver, lymph node and peritoneal metastases, with complete excision recommended (where possible and without major morbidity) if these are found. The position of any resected lesion should be marked to facilitate future radiotherapy. Normal lymph nodes of the hilum and peri vascular sites should also be biopsied and sent in individual containers to a pathologist (who has been pre-warned to expect the samples). Excision biopsy sampling of the hilar, and para-aortic lymph nodes should be undertaken, with clear separate labelling of samples. Lymph node sampling is critically important, despite the absence of abnormal nodes on pre-operative imaging, or upon gross inspection during operative exploration, since a review of lymph node sampling by the NWTS demonstrated a false negative rate of 31% and a false positive rate of 18% based on pre-operative and intra-operative assessment. Radical lymph node dissection, however, does not enhance survival and is not recommended. Intravascular extension of the tumour should be identified on pre-operative imaging, but the renal vein and IVC should also be carefully examined at an early stage of the operation. The Wilms tumour resection commences with dissection of the Gerota’s fascia to allow for displacement of the tumour anteriorly enabling safe dissection of the renal vessels. Where the tumour is of moderate size, early ligation of the vessels should be the aim. Kocher’s manoeuvre (displacement of the duodenum medially) may be helpful for both left and right tumours. In very extensive or adherent tumours, isolation of the hilar vessels prior to mobilization of the tumour may be theoretically desirable, but such vessels are frequently distorted and/or surrounded by tumour and such dissection risks major haemorrhage and/or damage to the aorta/IVC or major mesenteric or coeliac vessels. With modern imaging, tumour involvement of the renal vein or IVC should be known prior to surgery. In such cases, the dissection should be taken around the tumour first to allow for safe ligation of the vessels when possible. The renal artery should ideally be ligated first to avoid engorgement of the tumour. It is important that the vessels are ligated separately to avoid the possibility of a renal vessel vascular shunt and subsequent high output cardiac failure. Anomalous oncogenic vessels are frequently encountered originating from the psoas muscle together with a leash of neovascularity around the ureter and gonadal vesselse these should be sought and dealt with to maintain a bloodless field. Great care must be taken to avoid tumour rupture which potentially upstages the tumour from stage I to stage III. Some tumours have a thin capsule at risk of rupture, especially if they have not received prior chemotherapy (NWTS rupture rate 10% c.f. CCLG under 1%).
Stage II The tumour extends beyond kidney or penetrates through the renal capsule and/or fibrous pseudocapsule into perirenal fat but is completely resected (resection margins “clear”) Tumour infiltrates the renal sinus and/or invades blood and lymphatic vessels outside the renal parenchyma but it is completely resected Tumour infiltrates adjacent organs or vena cava but is completely resected Stage III Incomplete excision of the tumour, which extends beyond resection margins (gross or microscopical tumour remains post-operatively) - including non resection because tumour extends into vital structures Any abdominal lymph nodes are involved Tumour rupture before or intra-operatively (irrespective of other criteria for staging). The tumour has penetrated through the peritoneal surface Tumour implants are found on the peritoneal surface The tumour thrombi present at resection margins of vessels or ureter, transected or removed piecemeal by surgeon The tumour has been surgically biopsied (wedge biopsy) prior to pre-operative chemotherapy or surgery The presence of necrotic tumour or chemotherapy-induced changes in a lymph node or at the resection margins is regarded as proof of previous tumour with microscopic residue and therefore the tumour is assigned stage III (because of the possibility that some viable tumour is left behind in the adjacent lymph node or beyond resection margins.) Stage IV Haematogenous metastatic disease beyond stage III e e.g. lung, liver or bone. Stage V Bilateral disease. Each side should be staged according to the above criteria prior to surgery.
Surgical exploration Oncological surgeons should refresh their knowledge of the surgical protocols (SIOP or COG) prior to nephrectomy. Gross in 1953 established the principles of nephrectomy for paediatric malignancy. He recommended early ligation of the renal vessels, particularly the renal vein to avoid inadvertent displacement of a renal vein tumour embolus. With modern imaging, a venous embolus should be identified pre-operatively.
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Where required, “bench surgery” may be undertaken on the kidney to remove the tumour prior to re-implantation. Overall the results of such surgery have been satisfactory, although there have been reported complications of residual tumour left in situ, gross haematuria, and urinary leak (25%). For a partial nephrectomy, the aim should be to achieve a surrounding margin of healthy normal renal tissue e enucleation is not recommended.
The anatomy of the renal vessels is such that the left renal vein is far longer than the right, and on the whole a left tumour nephrectomy is far easier than a right. On many occasions with a large tumour, the right vein may be a thin wide strip stretched over the tumour. In such cases, a generous Kocher’s manoeuvre together with full dissection of the tumour prior to vein control should allow safe (double) ligation. Ligation must be secure, as a failed suture back on the ward would prove fatal before a child could be returned to theatre. The surgeon should avoid “tenting” the IVC during ligation to prevent an elliptical IVC breach when the suture falls back. It should also be within any oncological surgeon’s armamentarium that an IVC breach could be safely and swiftly corrected. Particular care should be taken to ensure that the correct ipsilateral renal vessel is the one being ligated. With very large tumours, the anatomy may be distorted such that the contralateral vessel is the first encountered. Clearly such an error would have disastrous consequences. The unilateral adrenal gland should be left in situ where the plain of dissection has not been breached by tumour. The ureter should be taken as close to the bladder as possible as Wilms tumour not infrequently invades down the ureter. Laparoscopic approach to nephroureterectomy is being reported, but an incision (e.g. pfannensteil) is still required, and the technique is only suitable for the smaller Wilms tumours. The larger tumours and those with renal hilar involvement should be resected by open technique. Some surgeons have extended laparoscopic resection to bilateral, stage 5 partial nephrectomies, again for the smaller nodules associated with nephroblastomatosis.
Contraindications for partial nephrectomy pre-operative tumour rupture or biopsy tumour infiltrating extra renal structures intra-abdominal metastases or lymph nodes seen on preoperative imaging thrombus in the renal vein or vena cava tumour involving more than 1/3 of the kidney (at least 50% of renal tissue should be spared after the tumour resection with a margin of healthy tissue, to give any worthwhile protection against hyper perfusion) multifocal tumour central location involvement of calyces haematuria little experience in partial nephrectomy
Lung metastases The management of a child with Wilms tumour should always be under a multidisciplinary oncological team (oncologists, surgeon, pathologist and radiotherapist). Where lung metastases are visible on chest CT scan following chemotherapy, there may be a role for surgical excision e either via open thoracotomy, or thoracoscopic resection. (the latter has the disadvantage that small metastases cannot be digitally felt). CT guide wire location prior to resection may be useful. Early surgical excision of lung metastases is reserved for those where the viability of pulmonary tumour is in doubt, and histological confirmation of necrotic or scar tissue would obviate lung radiation.
Tumour involving the renal vein, IVC Approximately 2e3% of children will present with tumour extension to the renal vein or IVC. The exact extent of the tumour should be determined pre-operatively with ultrasonography/ Doppler scans, echocardiography, CT and MRI scanning. A detailed plan for surgery should then be made. A short embolus in the renal vein may be resected along with the kidney. Tumour extending intrahepatically can be excised after proximal and distal control of the IVC is achieved. Where tumour extends to the level of the liver but remains infra-diaphragmatic, the liver may be mobilized medially (division of lateral ligaments) to allow control of the IVC posterior to the liver. Any tumour extending supra-diaphragmatically can be resected utilizing cardio-pulmonary bypass and deep hypothermia and circulatory arrest.
Bilateral e stage V e Wilms tumour Around 5% of children present with bilateral disease, particularly in those with a predisposing syndrome e WAGR, BeckwitheWiedermann, DenyseDrash. Around 90% of children should be able to be treated with bilateral partial nephrectomies. Nephron sparing surgery has been advocated for stage V tumours (to avoid the need for dialysis/transplant) but also for unilateral tumours to reduce the possibility of compensatory hypertrophy and decreased renal function over time Figure 4.
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Figure 4 Heminephrectomy for a right sided upper pole tumour. The vascular demarcation is shown after ligation of the right upper pole vessels.
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Bilateral pulmonary metastases may be approached by two thoracotomies, or a midline sternotomy as appropriate. The aim should be wedge radical excision or lobectomy if that is not feasible. A pneumonectomy is contra-indicated.
Jehovah’s witnesses Where the parents of a child with a nephroblastoma are Jehovah’s witnesses, clearly every care must be taken to avoid the need for a blood transfusion. Although in the UK a judicial ruling may be enforced to permit the giving of blood despite the parents’ wishes, in practice this is rarely necessary. Even with very large tumours, careful dissection, use of CUSA and bipolar dissection and red-cell saving will result in very little blood loss. The child may also be pre-prepared with erythropoietin and the use of AprotininÓ (Trasylol e SigmaeAldrich) per op will reduce capillary blood loss.
Early complications from Wilms nephrectomy The National Wilms tumour study group in the USA reported their results in 2001. They found that 12.7% of children had complications, including intestinal obstruction (5.1%), extensive haemorrhage (1.9%), wound infection (1.9%) and vascular injury (1.5%). Not surprisingly, complications were more likely if the tumour extended into the IVC or right atrium, but they were also seen more often when a flank incision was used rather than a lateral intraperitoneal approach. Other high risk factors included a tumour greater than 10 cm diameter ( p ¼ 0.05; OR 2), and when the surgery was performed by a general surgeon ( p ¼ 0.03, OR 9) rather than a paediatric surgeon. SIOP publications have shown that operative complications are reduced to under 8% if chemotherapy is given prior to surgery. Intestinal obstruction may be due to early postoperative ileus, which should settle on conservative management (gastric drainage and intravenous fluids/feeds) but may also be due to intussusception. Intussusception may be more common than is recognized and careful clinical and radiological examinations are required to avoid unnecessary sequelae. Early or late adhesion of the small bowel e usually down to the right paracolic gutter site of nephrectomy may require re-operation.
Figure 5 Excision of a large recurrent Wilms tumour via a thoracoabdominal approach.
Compensatory hypertrophy of the remaining contralateral kidney may develop to give proteinuria and reduced renal function due to focal glomerulosclerosis. This is exacerbated if the child has received radiotherapy that has extended over to the contralateral side. Experiments have shown hyperfiltration syndrome occurs if less than 25% renal mass remains (e.g. stage V, unilateral nephrectomy, contralateral partial nephrectomy) but it has also been seen clinically after only one kidney has been removed. End stage renal disease due to chronic renal failure 20 years after Wilms surgery has been reported in 0.7% of children. Early age at diagnosis, stroma predominant histology and bilateral tumours were risk factors. Should renal transplant be required, it has been recommended that at least 2 years disease free survival
Surgical treatment of relapse The success rate of treatment of first relapse is high and the intention should be to cure. Initial management is with second line chemotherapy, with surgical resection where relapse sites allow after a response to chemotherapy has been shown. The aim should be complete resection with titanium clip identification of sites to focus subsequent radiotherapy Figure 5.
Long term outcomes from surgery As the cure rate for Wilms tumours in childhood has increased, the long term effects of the surgery and adjuvant treatment are becoming more obvious. Most of these are due to the effects of radiotherapy (above 1200 cGy) and/or chemotherapy (ifosfamide, etoposide), but nephrectomy in an infant can lead to compensatory hypertrophy and hyperfiltration syndrome.
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Figure 6 Excision of a right Wilms tumour.
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Javid PJ, Lendvay TS, Aclerno S, Gow KW. Laparoscopic nephroureterectomy for Wilms tumour: oncologic considerations. J Pediatr Surg 2011; 46: 978e82. Mitchell C, Pritchard-Jones K, Shannon R, et al. United Kingdom Cancer Study Group. Immediate nephrectomy versus pre-operative chemotherapy in the management of non metastatic Wilms tumour: results of a randomised trial (UKW3) by the UK children’s cancer study group. Eur J Cancer 2006; 42: 2554e62. Pritchard-Jones K, Moroz V, Vujanic G, et al. Children’s Cancer and Leukaemia Group (CCLG) Renal Tumours Group. Treatment and outcome of Wilms tumour patients: an analysis of all cases registered in the UKW3 trial. Ann Oncol 2012; 23: 2457e63. Rauth TP, Slone J, Crane G, Correa H, Friedman DL, Lovvorn 3rd HN. Laparoscopic nephron-sparing resection of synchronous Wilms tumors in a case of hyperplastic perilobar nephroblastomatosis. J Pediatr Surg 2011; 46: 983e8. Ritchey ML, Kelasis PP, Breslow N, et al. Surgical complications following nephrectomy for Wilms tumour: a report of the national Wilms tumour study-3. Surg Gyn Obst 1992; 175: 507e14. Ritchey ML, Shamberger RC, Haase G, Horwitz J, Bergemann T, Breslow NE. Surgical complications after primary nephrectomy for Wilms tumor: report from the National Wilms tumor study group. J Am Coll Surg 2001; 192: 63e8. Ritchey ML. Nephron sparing surgery for Wilms tumour e where is the future? J Urol 2011; 186: 1179e80. Shamberger RC, Guthrie KA, Richey ML, et al. Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study. Ann Surg 1999; 229: 292e7. Sulkowski J, Kolon T, Mattei P. Nephron-sparing partial nephrectomy for bilateral Wilms tumor. J Pediatr Surg 2012 Jun; 47: 1234e8. Varlet F, Stephen JL, Guye R, et al. Laparoscopic radical nephrectomy for unilateral renal cancer in children. Surg Laparosc Endosc Percutan Tech 2009; 19: 148e52.
occurs first to avoid increasing the risk of immunosuppression metastases.
Conclusion Complete surgical excision of a Wilms tumour is an essential component of the management of this malignancy. With successful surgery, complications should be below 10% and overall survival over 90%. Such surgery may be challenging and should be concentrated to those few surgeons in the UK who perform more than five or six cases per year Figure 6. A
FURTHER READING Bader MI, Abdelaal K, Rogers T, Arul S. A surgical approach to Wilms tumour with retrohepatic vena caval extension. Pediatr Surg Int 2013; 29: 229e32. 2. Cozzi DA, Schiavetti A, Morini F, Castello MA, Cozzi F. Nephron-sparing surgery for unilateral primary renal tumor in children. J Pediatr Surg 2001 Feb; 36: 362e5. Davidoff AM, Giel DW, Jones DP, et al. The feasibility and outcome of nephron-sparing surgery for children with bilateral Wilms tumor. The St Jude Children’s Research Hospital experience: 1999e2006. Cancer 2008 May 1; 112: 2060e70. Federici S, Ratta A, Mordenti M, et al. Successful thoracoscopic resection of pulmonary metastasis less than 1 cm. J Laparoendosc Adv Surg Tech 2009; 19: 171e3. Gow KW, Barnhart DC, Hamilton TE, et al. Primary nephrectomy and intraoperative tumor spill: report from the Children’s Oncology Group (COG) renal tumors committee. J Pediatr Surg 2013 Jan; 48: 34e8. Gross RE. The surgery of infancy and childhood. Philadelphia: WB Saunders Co, 1953.
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Wilms tumour e the surgical issues
receive regular USS scans of their kidneys. Thus, asymptomatic tumours may be identified at an early stage. Rarely the tumour may rupture following relatively minor trauma e or present as cardiac arrhythmia or fatal pulmonary embolus e see Figure 2.
Simon N Huddart
Differential diagnosis Whilst 90% of the renal tumours of childhood are Wilms, rhabdoid tumour and clear cell carcinoma may also occur. The prognosis for these two latter is worse than that for Wilms, but the surgery is essentially the same. Diagnosis should be confirmed by Trucut biopsy to ensure appropriate chemotherapy regimens are employed. Congenital mesoblastic nephroma accounts for 2% of renal tumours, usually in infancy and carries a good prognosis following successful surgery. Xanthogranulomatous pyelonephritis (XGP) is a benign chronic inflammation of the kidney, which may present with fever and anaemia. The renal mass can usually be distinguished from Wilms tumour on ultrasound, but a Trucut biopsy may be required. One criticism of the original SIOP guidelines (Chemotherapy without biopsy) was that chemotherapy was given prior to open surgery without prior Trucut biopsy. A very small number of XGP cases or clear cell tumours etc were therefore liable to be erroneously treated. Other tumours which may present as a right renal mass include: Neuroblastoma e urinary catecholamines are usually raised. Hepatoblastoma e should be identifiable on USS. Teratoma e may have raised Alfa feto-protein and/or HCG. Whilst benign conditions such as Pelviureteric junction obstruction may present as a large renal mass, a USS should distinguish these from malignancy.
Abstract Complete surgical excision is an essential component of the management of Wilms tumour. With successful surgery, complications should be below 10% and overall survival over 90%. Such surgery may be challenging and should be concentrated to those few surgeons in the UK who perform more than five or six cases per year.
Keywords CCLG; excision; nephrectomy; nephroblastoma; SIOP; Wilms
Introduction Nephroblastoma was first described by Max Wilms in 1899. Before multimodal therapy, surgery was the only option and survival rates were fewer than one in five. Despite the introduction of effective chemotherapy and radiotherapy (for advanced stages) surgery still remains an essential element of the management. Today with surgery and adjuvant chemo/radiotherapy, survival is over 87%. Per and perioperative deaths are very rare except when large tumours present ruptured following trauma. Surgery for a Wilms tumour is seldom an emergency and can be challenging. The most experienced oncological specialist paediatric surgeon available should undertake it and care of the child should be under a multidisciplinary paediatric oncology team.
Diagnosis The majority of Wilms tumours are asymptomatic for the early course of the disease e thus the tumours may present very large. Often it is the parent or clinician who identifies a large lateral mass during bath time or routine examination respectively. Like several of the large tumours of infancy, Nephroblastoma may present as malaise and loss of energy with a slowly enlarging abdominal mass e late or mis-diagnosis is not uncommon. Less commonly, haematuria (15%), abdominal pain (10%) fever (20%) or hypertension (10%) is the presenting complaint. Classically also, a left Wilms tumour may present as a left varicocele due to tumour effects on the renal vein (into which the gonadal vein is a tributary) e see Figure 1. Children with predisposing conditions such as Beckwithe Wiedermann, hemihypertrophy, Aniridia (Wilms tumour, aniridia, genitourinary anomalies, mental retardation e WAGR) or Denys Drash (nephrotic syndrome, ambiguous genitalia) should
Pre-op investigations Oncological USS e usually correctly identifies the Wilms diagnosis. Pre-operative plain chest X-ray in two planes (pulmonary metastases). CT e further identifies pulmonary metastases, confirms normality of contralateral kidney, may identify nephroblastomatosis, should identify venous tumour extension Figure 3. MRI e further delineates venous extension. AFP/HCG e to exclude malignant teratoma. 24 hour Urinary catecholamines e to exclude neuroblastoma. Trucut biopsy This is strongly advised in the UK to obtain tissue diagnosis prior to pre-operative chemotherapy (usually 6 weeks). Several cores of 12e14G are recommended under USS control. Consideration should be given to siting the biopsy entry wound where it can be excised in the nephrectomy procedure.
Simon N Huddart MA MBBS FRCS FRCS(Paeds) Consultant Paediatric Surgeon, Department of Paediatric Surgery, University Hospital of Wales, Cardiff, UK. Conflict of interest: none declared.
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Figure 3 CT scan of large left sided Wilms tumour e no venous involvement is shown.
The trial favoured prior treatment with chemotherapy e intraoperative rupture was reduced from 15% to essentially zero, there was less blood loss and stage II and III tumours were downgraded. In the USA, surgery is performed as initial management of the tumour, and then chemotherapy/radiotherapy is given dependant on stage and histology. The advantage is that a “true” stage of tumour at presentation is achieved and histology is not affected by prior chemotherapy. The main disadvantages are an increase in the risk of tumour rupture at surgery, which can upstage a stage I tumour to stage III. Gow et al recently reported the results of the Children’s Oncology Group renal tumours committee. Of 1,131 primary nephrectomies, tumour spill occurred in 9.7%, with an additional 1.8% having possible spill during renal vein or IVC tumour nephrectomy. Large tumours (more than12 cm) and those on the right were more at risk. As surgery is only an emergency in the rare cases of tumour rupture with uncontrolled bleeding, in the majority of cases, surgery should be a planned procedure by the most experienced surgical team available. The surgeon should make themselves familiar with the various aspects of the SIOP surgical protocol prior to the operation: Computerized tomography e CT and ultrasound scans of the tumour(s) should be studied prior to the operation. In particular, any suspicious hilar or para-aortic lymph nodes should be noted with a view to excision biopsy. Also, any tumour involvement of the renal vein or IVC should be identified (vide infra).
Figure 1 A left sided varicocele in a 2-year-old boy with a large left sided Wilms tumour.
In the United Kingdom and most of Europe, the protocol of SIOP (Societe Internationale Oncologie D’Pediatrique) will be followed. In this protocol, the diagnosis of Wilms and whether it is favourable or unfavourable histology is first confirmed by Trucut biopsy samples taken under ultrasound guidance. The chemotherapy regimen is given pre resection appropriate to the tumour stage and histology. (Fine needle aspiration or Trucut biopsy does not upstage the tumour). A 10-year-trial in the United Kingdom was completed in 2001. UKW3 randomizing early stage Wilms to primary surgery or surgery post 6 weeks of Vincristine.
Staging of Wilms tumour Stage I The tumour is limited to the kidney or surrounded with a fibrous capsule if outside the normal contours of the kidney. The renal capsule or pseudocapsule may be infiltrated with the tumour but it does not reach the outer surface, and it is completely resected (resection margins “clear’) The tumour may be protruding (“bulging’) into the pelvic system and “dipping’ into the ureter (but it is not infiltrating their walls)
Figure 2 Post mortem finding of a massive Wilms tumour embolus.
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The vessels of the renal sinus are not involved Intrarenal vessel involvement may be present Fine needle aspiration or percutaneous core needle biopsy (Trucut) does not upstage the tumour. The presence of necrotic tumour or chemotherapy-induced change in the renal sinus and/or within the peri-renal fat should not be regarded as a reason for upstaging a tumour providing it is completely excised and does not reach the resection margins.
Except in the rare case of tumour rupture, the nephrectomy is an elective operation and should be carried out by the most experienced surgical team. A generous transverse, transperitoneal abdominal incision on the side of the tumour is recommended e although if the CT scan clearly shows no involvement of the contralateral side, it is no longer necessary to physically explore the other kidney. The needle tract of the Trucut biopsy site should be included in the surgical wound resection. The abdomen should be examined for liver, lymph node and peritoneal metastases, with complete excision recommended (where possible and without major morbidity) if these are found. The position of any resected lesion should be marked to facilitate future radiotherapy. Normal lymph nodes of the hilum and peri vascular sites should also be biopsied and sent in individual containers to a pathologist (who has been pre-warned to expect the samples). Excision biopsy sampling of the hilar, and para-aortic lymph nodes should be undertaken, with clear separate labelling of samples. Lymph node sampling is critically important, despite the absence of abnormal nodes on pre-operative imaging, or upon gross inspection during operative exploration, since a review of lymph node sampling by the NWTS demonstrated a false negative rate of 31% and a false positive rate of 18% based on pre-operative and intra-operative assessment. Radical lymph node dissection, however, does not enhance survival and is not recommended. Intravascular extension of the tumour should be identified on pre-operative imaging, but the renal vein and IVC should also be carefully examined at an early stage of the operation. The Wilms tumour resection commences with dissection of the Gerota’s fascia to allow for displacement of the tumour anteriorly enabling safe dissection of the renal vessels. Where the tumour is of moderate size, early ligation of the vessels should be the aim. Kocher’s manoeuvre (displacement of the duodenum medially) may be helpful for both left and right tumours. In very extensive or adherent tumours, isolation of the hilar vessels prior to mobilization of the tumour may be theoretically desirable, but such vessels are frequently distorted and/or surrounded by tumour and such dissection risks major haemorrhage and/or damage to the aorta/IVC or major mesenteric or coeliac vessels. With modern imaging, tumour involvement of the renal vein or IVC should be known prior to surgery. In such cases, the dissection should be taken around the tumour first to allow for safe ligation of the vessels when possible. The renal artery should ideally be ligated first to avoid engorgement of the tumour. It is important that the vessels are ligated separately to avoid the possibility of a renal vessel vascular shunt and subsequent high output cardiac failure. Anomalous oncogenic vessels are frequently encountered originating from the psoas muscle together with a leash of neovascularity around the ureter and gonadal vesselse these should be sought and dealt with to maintain a bloodless field. Great care must be taken to avoid tumour rupture which potentially upstages the tumour from stage I to stage III. Some tumours have a thin capsule at risk of rupture, especially if they have not received prior chemotherapy (NWTS rupture rate 10% c.f. CCLG under 1%).
Stage II The tumour extends beyond kidney or penetrates through the renal capsule and/or fibrous pseudocapsule into perirenal fat but is completely resected (resection margins “clear”) Tumour infiltrates the renal sinus and/or invades blood and lymphatic vessels outside the renal parenchyma but it is completely resected Tumour infiltrates adjacent organs or vena cava but is completely resected Stage III Incomplete excision of the tumour, which extends beyond resection margins (gross or microscopical tumour remains post-operatively) - including non resection because tumour extends into vital structures Any abdominal lymph nodes are involved Tumour rupture before or intra-operatively (irrespective of other criteria for staging). The tumour has penetrated through the peritoneal surface Tumour implants are found on the peritoneal surface The tumour thrombi present at resection margins of vessels or ureter, transected or removed piecemeal by surgeon The tumour has been surgically biopsied (wedge biopsy) prior to pre-operative chemotherapy or surgery The presence of necrotic tumour or chemotherapy-induced changes in a lymph node or at the resection margins is regarded as proof of previous tumour with microscopic residue and therefore the tumour is assigned stage III (because of the possibility that some viable tumour is left behind in the adjacent lymph node or beyond resection margins.) Stage IV Haematogenous metastatic disease beyond stage III e e.g. lung, liver or bone. Stage V Bilateral disease. Each side should be staged according to the above criteria prior to surgery.
Surgical exploration Oncological surgeons should refresh their knowledge of the surgical protocols (SIOP or COG) prior to nephrectomy. Gross in 1953 established the principles of nephrectomy for paediatric malignancy. He recommended early ligation of the renal vessels, particularly the renal vein to avoid inadvertent displacement of a renal vein tumour embolus. With modern imaging, a venous embolus should be identified pre-operatively.
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Where required, “bench surgery” may be undertaken on the kidney to remove the tumour prior to re-implantation. Overall the results of such surgery have been satisfactory, although there have been reported complications of residual tumour left in situ, gross haematuria, and urinary leak (25%). For a partial nephrectomy, the aim should be to achieve a surrounding margin of healthy normal renal tissue e enucleation is not recommended.
The anatomy of the renal vessels is such that the left renal vein is far longer than the right, and on the whole a left tumour nephrectomy is far easier than a right. On many occasions with a large tumour, the right vein may be a thin wide strip stretched over the tumour. In such cases, a generous Kocher’s manoeuvre together with full dissection of the tumour prior to vein control should allow safe (double) ligation. Ligation must be secure, as a failed suture back on the ward would prove fatal before a child could be returned to theatre. The surgeon should avoid “tenting” the IVC during ligation to prevent an elliptical IVC breach when the suture falls back. It should also be within any oncological surgeon’s armamentarium that an IVC breach could be safely and swiftly corrected. Particular care should be taken to ensure that the correct ipsilateral renal vessel is the one being ligated. With very large tumours, the anatomy may be distorted such that the contralateral vessel is the first encountered. Clearly such an error would have disastrous consequences. The unilateral adrenal gland should be left in situ where the plain of dissection has not been breached by tumour. The ureter should be taken as close to the bladder as possible as Wilms tumour not infrequently invades down the ureter. Laparoscopic approach to nephroureterectomy is being reported, but an incision (e.g. pfannensteil) is still required, and the technique is only suitable for the smaller Wilms tumours. The larger tumours and those with renal hilar involvement should be resected by open technique. Some surgeons have extended laparoscopic resection to bilateral, stage 5 partial nephrectomies, again for the smaller nodules associated with nephroblastomatosis.
Contraindications for partial nephrectomy pre-operative tumour rupture or biopsy tumour infiltrating extra renal structures intra-abdominal metastases or lymph nodes seen on preoperative imaging thrombus in the renal vein or vena cava tumour involving more than 1/3 of the kidney (at least 50% of renal tissue should be spared after the tumour resection with a margin of healthy tissue, to give any worthwhile protection against hyper perfusion) multifocal tumour central location involvement of calyces haematuria little experience in partial nephrectomy
Lung metastases The management of a child with Wilms tumour should always be under a multidisciplinary oncological team (oncologists, surgeon, pathologist and radiotherapist). Where lung metastases are visible on chest CT scan following chemotherapy, there may be a role for surgical excision e either via open thoracotomy, or thoracoscopic resection. (the latter has the disadvantage that small metastases cannot be digitally felt). CT guide wire location prior to resection may be useful. Early surgical excision of lung metastases is reserved for those where the viability of pulmonary tumour is in doubt, and histological confirmation of necrotic or scar tissue would obviate lung radiation.
Tumour involving the renal vein, IVC Approximately 2e3% of children will present with tumour extension to the renal vein or IVC. The exact extent of the tumour should be determined pre-operatively with ultrasonography/ Doppler scans, echocardiography, CT and MRI scanning. A detailed plan for surgery should then be made. A short embolus in the renal vein may be resected along with the kidney. Tumour extending intrahepatically can be excised after proximal and distal control of the IVC is achieved. Where tumour extends to the level of the liver but remains infra-diaphragmatic, the liver may be mobilized medially (division of lateral ligaments) to allow control of the IVC posterior to the liver. Any tumour extending supra-diaphragmatically can be resected utilizing cardio-pulmonary bypass and deep hypothermia and circulatory arrest.
Bilateral e stage V e Wilms tumour Around 5% of children present with bilateral disease, particularly in those with a predisposing syndrome e WAGR, BeckwitheWiedermann, DenyseDrash. Around 90% of children should be able to be treated with bilateral partial nephrectomies. Nephron sparing surgery has been advocated for stage V tumours (to avoid the need for dialysis/transplant) but also for unilateral tumours to reduce the possibility of compensatory hypertrophy and decreased renal function over time Figure 4.
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Figure 4 Heminephrectomy for a right sided upper pole tumour. The vascular demarcation is shown after ligation of the right upper pole vessels.
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Bilateral pulmonary metastases may be approached by two thoracotomies, or a midline sternotomy as appropriate. The aim should be wedge radical excision or lobectomy if that is not feasible. A pneumonectomy is contra-indicated.
Jehovah’s witnesses Where the parents of a child with a nephroblastoma are Jehovah’s witnesses, clearly every care must be taken to avoid the need for a blood transfusion. Although in the UK a judicial ruling may be enforced to permit the giving of blood despite the parents’ wishes, in practice this is rarely necessary. Even with very large tumours, careful dissection, use of CUSA and bipolar dissection and red-cell saving will result in very little blood loss. The child may also be pre-prepared with erythropoietin and the use of AprotininÓ (Trasylol e SigmaeAldrich) per op will reduce capillary blood loss.
Early complications from Wilms nephrectomy The National Wilms tumour study group in the USA reported their results in 2001. They found that 12.7% of children had complications, including intestinal obstruction (5.1%), extensive haemorrhage (1.9%), wound infection (1.9%) and vascular injury (1.5%). Not surprisingly, complications were more likely if the tumour extended into the IVC or right atrium, but they were also seen more often when a flank incision was used rather than a lateral intraperitoneal approach. Other high risk factors included a tumour greater than 10 cm diameter ( p ¼ 0.05; OR 2), and when the surgery was performed by a general surgeon ( p ¼ 0.03, OR 9) rather than a paediatric surgeon. SIOP publications have shown that operative complications are reduced to under 8% if chemotherapy is given prior to surgery. Intestinal obstruction may be due to early postoperative ileus, which should settle on conservative management (gastric drainage and intravenous fluids/feeds) but may also be due to intussusception. Intussusception may be more common than is recognized and careful clinical and radiological examinations are required to avoid unnecessary sequelae. Early or late adhesion of the small bowel e usually down to the right paracolic gutter site of nephrectomy may require re-operation.
Figure 5 Excision of a large recurrent Wilms tumour via a thoracoabdominal approach.
Compensatory hypertrophy of the remaining contralateral kidney may develop to give proteinuria and reduced renal function due to focal glomerulosclerosis. This is exacerbated if the child has received radiotherapy that has extended over to the contralateral side. Experiments have shown hyperfiltration syndrome occurs if less than 25% renal mass remains (e.g. stage V, unilateral nephrectomy, contralateral partial nephrectomy) but it has also been seen clinically after only one kidney has been removed. End stage renal disease due to chronic renal failure 20 years after Wilms surgery has been reported in 0.7% of children. Early age at diagnosis, stroma predominant histology and bilateral tumours were risk factors. Should renal transplant be required, it has been recommended that at least 2 years disease free survival
Surgical treatment of relapse The success rate of treatment of first relapse is high and the intention should be to cure. Initial management is with second line chemotherapy, with surgical resection where relapse sites allow after a response to chemotherapy has been shown. The aim should be complete resection with titanium clip identification of sites to focus subsequent radiotherapy Figure 5.
Long term outcomes from surgery As the cure rate for Wilms tumours in childhood has increased, the long term effects of the surgery and adjuvant treatment are becoming more obvious. Most of these are due to the effects of radiotherapy (above 1200 cGy) and/or chemotherapy (ifosfamide, etoposide), but nephrectomy in an infant can lead to compensatory hypertrophy and hyperfiltration syndrome.
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Figure 6 Excision of a right Wilms tumour.
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Javid PJ, Lendvay TS, Aclerno S, Gow KW. Laparoscopic nephroureterectomy for Wilms tumour: oncologic considerations. J Pediatr Surg 2011; 46: 978e82. Mitchell C, Pritchard-Jones K, Shannon R, et al. United Kingdom Cancer Study Group. Immediate nephrectomy versus pre-operative chemotherapy in the management of non metastatic Wilms tumour: results of a randomised trial (UKW3) by the UK children’s cancer study group. Eur J Cancer 2006; 42: 2554e62. Pritchard-Jones K, Moroz V, Vujanic G, et al. Children’s Cancer and Leukaemia Group (CCLG) Renal Tumours Group. Treatment and outcome of Wilms tumour patients: an analysis of all cases registered in the UKW3 trial. Ann Oncol 2012; 23: 2457e63. Rauth TP, Slone J, Crane G, Correa H, Friedman DL, Lovvorn 3rd HN. Laparoscopic nephron-sparing resection of synchronous Wilms tumors in a case of hyperplastic perilobar nephroblastomatosis. J Pediatr Surg 2011; 46: 983e8. Ritchey ML, Kelasis PP, Breslow N, et al. Surgical complications following nephrectomy for Wilms tumour: a report of the national Wilms tumour study-3. Surg Gyn Obst 1992; 175: 507e14. Ritchey ML, Shamberger RC, Haase G, Horwitz J, Bergemann T, Breslow NE. Surgical complications after primary nephrectomy for Wilms tumor: report from the National Wilms tumor study group. J Am Coll Surg 2001; 192: 63e8. Ritchey ML. Nephron sparing surgery for Wilms tumour e where is the future? J Urol 2011; 186: 1179e80. Shamberger RC, Guthrie KA, Richey ML, et al. Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study. Ann Surg 1999; 229: 292e7. Sulkowski J, Kolon T, Mattei P. Nephron-sparing partial nephrectomy for bilateral Wilms tumor. J Pediatr Surg 2012 Jun; 47: 1234e8. Varlet F, Stephen JL, Guye R, et al. Laparoscopic radical nephrectomy for unilateral renal cancer in children. Surg Laparosc Endosc Percutan Tech 2009; 19: 148e52.
occurs first to avoid increasing the risk of immunosuppression metastases.
Conclusion Complete surgical excision of a Wilms tumour is an essential component of the management of this malignancy. With successful surgery, complications should be below 10% and overall survival over 90%. Such surgery may be challenging and should be concentrated to those few surgeons in the UK who perform more than five or six cases per year Figure 6. A
FURTHER READING Bader MI, Abdelaal K, Rogers T, Arul S. A surgical approach to Wilms tumour with retrohepatic vena caval extension. Pediatr Surg Int 2013; 29: 229e32. 2. Cozzi DA, Schiavetti A, Morini F, Castello MA, Cozzi F. Nephron-sparing surgery for unilateral primary renal tumor in children. J Pediatr Surg 2001 Feb; 36: 362e5. Davidoff AM, Giel DW, Jones DP, et al. The feasibility and outcome of nephron-sparing surgery for children with bilateral Wilms tumor. The St Jude Children’s Research Hospital experience: 1999e2006. Cancer 2008 May 1; 112: 2060e70. Federici S, Ratta A, Mordenti M, et al. Successful thoracoscopic resection of pulmonary metastasis less than 1 cm. J Laparoendosc Adv Surg Tech 2009; 19: 171e3. Gow KW, Barnhart DC, Hamilton TE, et al. Primary nephrectomy and intraoperative tumor spill: report from the Children’s Oncology Group (COG) renal tumors committee. J Pediatr Surg 2013 Jan; 48: 34e8. Gross RE. The surgery of infancy and childhood. Philadelphia: WB Saunders Co, 1953.
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